Riley D C, Bittner G D, Mikesh M, Cardwell N L, Pollins A C, Ghergherehchi C L, Bhupanapadu Sunkesula S R, Ha T N, Hall B T D, Poon A D, Pyarali M, Boyer R B, Mazal A T, Munoz N, Trevino R C, Schallert T, Thayer W P
Department of Plastic Surgery, Vanderbilt School of Medicine, Nashville, Tennessee; Department of Neuroscience, University of Texas at Austin, Austin, Texas.
J Neurosci Res. 2015 Apr;93(4):572-83. doi: 10.1002/jnr.23514. Epub 2014 Nov 25.
Restoration of neuronal functions by outgrowths regenerating at ∼1 mm/day from the proximal stumps of severed peripheral nerves takes many weeks or months, if it occurs at all, especially after ablation of nerve segments. Distal segments of severed axons typically degenerate in 1-3 days. This study shows that Wallerian degeneration can be prevented or retarded, and lost behavioral function can be restored, following ablation of 0.5-1-cm segments of rat sciatic nerves in host animals. This is achieved by using 0.8-1.1-cm microsutured donor allografts treated with bioengineered solutions varying in ionic and polyethylene glycol (PEG) concentrations (modified PEG-fusion procedure), being careful not to stretch any portion of donor or host sciatic nerves. The data show that PEG fusion permanently restores axonal continuity within minutes, as initially assessed by action potential conduction and intracellular diffusion of dye. Behavioral functions mediated by the sciatic nerve are largely restored within 2-4 weeks, as measured by the sciatic functional index. Increased restoration of sciatic behavioral functions after ablating 0.5-1-cm segments is associated with greater numbers of viable myelinated axons within and distal to PEG-fused allografts. Many such viable myelinated axons are almost certainly spared from Wallerian degeneration by PEG fusion. PEG fusion of donor allografts may produce a paradigm shift in the treatment of peripheral nerve injuries.
如果确实发生的话,从切断的外周神经近端残端以每天约1毫米的速度再生出的神经突来恢复神经元功能需要数周或数月,尤其是在神经节段切除后。切断轴突的远端部分通常在1 - 3天内退化。本研究表明,在宿主动物中切除0.5 - 1厘米长的大鼠坐骨神经节段后,华勒氏变性可以被预防或延缓,并且丧失的行为功能可以恢复。这是通过使用经离子和聚乙二醇(PEG)浓度不同的生物工程溶液处理的0.8 - 1.1厘米的显微缝合供体同种异体移植物来实现的(改良的PEG融合程序),同时要小心避免拉伸供体或宿主坐骨神经的任何部分。数据显示,PEG融合在数分钟内就能永久恢复轴突的连续性,这最初是通过动作电位传导和染料的细胞内扩散来评估的。通过坐骨神经功能指数测量,由坐骨神经介导的行为功能在2 - 4周内基本恢复。切除0.5 - 1厘米节段后坐骨神经行为功能恢复的增加与PEG融合的同种异体移植物内及其远端有更多存活的有髓轴突有关。许多这样存活的有髓轴突几乎肯定因PEG融合而免于华勒氏变性。供体同种异体移植物的PEG融合可能会在外周神经损伤的治疗中引发范式转变。